rs11814680

chr10-112670447-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145206.4(VTI1A):c.560+1449C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,062 control chromosomes in the GnomAD database, including 6,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (6832 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

Genes affected

VTI1A (HGNC:17792): (vesicle transport through interaction with t-SNAREs 1A) The protein encoded by this gene is a member of the family of soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNAREs) that function in intracellular trafficking. This family member is involved in vesicular transport between endosomes and the trans-Golgi network. It is a vesicle-associated SNARE (v-SNARE) that interacts with target membrane SNAREs (t-SNAREs). Polymorphisms in this gene have been associated with binocular function, and also with susceptibility to colorectal and lung cancers. A recurrent rearrangement has been found between this gene and the transcription factor 7-like 2 (TCF7L2) gene in colorectal cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VTI1A	NM_145206.4	c.560+1449C>A		intron_variant		ENST00000393077.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTI1A	ENST00000393077.3	c.560+1449C>A		intron_variant		2	NM_145206.4	P4
VTI1A	ENST00000432306.5	c.560+1449C>A		intron_variant		1
VTI1A	ENST00000705995.1	c.581+1449C>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36908 AN: 151944 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152062 Hom.: 6832 Cov.: 32 AF XY: 0.236 AC XY: 17567 AN XY: 74336

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0870

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.222

Alfa AF: 0.163 Hom.: 2418

Bravo AF: 0.262

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	14
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11814680; hg19: chr10-114430206; COSMIC: COSV67580788; COSMIC: COSV67580788;